The proposed research will investigate the requirement for induction of a protective immune response to Salmonella infection in C3H/HeJ mice, a strain which is genetically deficient in their responsiveness to phenol-water purified lipopolysaccharides of Gram-negative bacteria. Results will be compared with responses in histocompatible normal C3HeB/FeJ mice. Experiments will correlate protection induced by various Salmonella vaccines and by other natural products with in vivo measurements of humoral and cellular immunity. The in vivo activity of the various Salmonella preparations will be further correlated with their ability to generate in vitro immune responses, both specific for O antigens and non-specific (to sheep red blood cells and other antigens) and with their mitogenicity. Materials to be studied in detail will be Salmonella lipopolysaccharide prepared by different methods, mitogenic protein fractions of Gram-negative bacteria. It is anticipated that the results will provide insight into the molecular requirements for secretion of anti-O antibody by murine B cells, into the role of ribonucleic acids in anti-O antibody secretion and in development of anti-Salmonella immunity, and into the nature of the antigens and/or the mitogenic factors necessary for development of anti-Salmonella immunity.